Fueled by up to $8.8 million in funding from the National Institute of Standards and Technology, BioNanomatrix and Complete Genomics, startups on opposite coasts, are combining their platforms to build a sequencer that will enable not the $1,000 genome, but the $100 genome.
Both companies, which will collectively match the grant with their own funding, are working on nearer-term applications for their respective technologies on their own. But the five-year grant, awarded under NIST’s Advanced Technology Program, which funds high-risk industrial research projects, will allow BioNanomatrix’s nanofluidic DNA imaging device and Complete Genomics’ sequencing chemistry to find a way to work in tandem.
The current crop of new sequencing technologies is “squeezing as much data out of existing biochemistries, existing optics approaches, as they can ... but the challenge is that they are not really breaking through the barriers in terms of cost, throughput, and accuracy,” said BioNanomatrix’s president and CEO Michael Boyce-Jacino. That, he believes, will be possible with these two platforms.
BioNanomatrix, a spinout from Princeton University that is based in Philadelphia, has developed a nanofluidic device for linearizing and imaging DNA. The chip carries an array of nanochannels, each 100 nanometers or less in diameter. These channels take up and stretch out single molecules of genomic DNA that can be imaged at high resolution using “relatively standard optics strategies,” according to Boyce-Jacino.
A former vice president of global genomics at Beckman Coulter and CSO of Orchid Biosciences, Boyce-Jacino has known Complete Genomics’ CSO Rade Drmanac for about 15 years. Drmanac, a founder of Hyseq and president and CSO of its spin-off, Callida Genomics, founded Complete Genomics last year in order to develop a low-cost DNA sequencing technology.
“We talked about our personal general interest in DNA sequencing and the challenges, and we saw this as an opportunity to collectively push the limits of our technologies and see really how much we can get out of it,” Boyce-Jacino said.
The plan is to detect fluorescent probes from Complete Genomics’ sequencing chemistry using genomic DNA spread out on BioNanomatrix’ device. The advantage of this approach, according to the companies, is the combination of local sequence information with long-range information about its position in the genome. “Duplicated genes in short pieces are really hard to tell apart, but if you see them next to each other in a linear fashion, you really know what’s going on and where your data is coming from,” Boyce-Jacino said.
Other advantages include the fact that sequencing long single molecules would mean simple sample prep, and that the technology can also provide haplotype information. “Everybody is forgetting that cells have two complements, one from each parent,” Drmanac said. “Knowing the consensus is not enough, especially for diagnostics.”
Complete Genomics is currently mum about the nature of its sequencing chemistry, describing it as “fluorescently labeled chemical ‘keyword’ probes specially designed for long DNA molecules.” The approach is not based on sequencing by synthesis, though, where one base is read at a time. “We focus on the expertise that we have starting with sequencing by hybridization 20 years ago,” Drmanac said. “[We] read words, but we have many different chemistries to read words, not just one chemistry.”
Current sequencing technologies are “squeezing as much data out of existing biochemistries, existing optics approaches, as they can ... but the challenge is that they are not really breaking through the barriers in terms of cost, throughput, and accuracy.”
“One reason it’s a good partnership is, [Complete Genomics] is extremely good at generating and processing genomes’ worth of data,” Boyce-Jacino said. “That’s a real strength that they bring to the table.”
At the end of the five-year ATP project, the two partners want to have a commercial sequencing device at hand. But that is still a long way ahead. “The challenge will really be bringing those two things together, and making sure that we understand the flow rates and the processing rates and the ideal size of fragments of DNA that we want to look at, the ideal optics and chemistry approaches,” Boyce-Jacino said. “We will explore a number of different combinations of these parameters to get the system to work well.”
The ultimate goal is to create a platform that is able to sequence a complete human genome with accuracy that exceeds today’s standards for $100. “The reason we have an aggressive cost target is that we want to make it accessible to clinical diagnostics,” Boyce-Jacino said.
“Today, the conventional wisdom is you do screening with SNP chips,” explained Cliff Reid, Complete Genomics’ CEO. But these chips only cover common SNPs, which are just a subset of the genomic variation that might be medically relevant. “That’s what the $100 genome provides,” he said.
It was not immediately clear how the companies’ technologies will allow them to reach this ambitious goal.
For Complete Genomics, the partnership with BioNanomatrix is only one way to bring its sequencing technology to market. Near term, it wants to commercialize its sequencing chemistry on its own and plans to reveal details about it early next year.
In March, Complete Genomics raised more than $6 million in a second funding round from new investor Prospect Venture Partners and existing investors OVP Venture Partners and Enterprise Partners Venture. The company received $6 million in seed funding last year from OVP and Enterprise.